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Hairpin Peptides (hairpin + peptide)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Effects of Chain Length and N-Methylation on a Cation,, Interaction in a ,-Hairpin Peptide

CHEMISTRY - A EUROPEAN JOURNAL, Issue 20 2007
Robert
Abstract The effects of N-methylation and chain length on a cation,, interaction have been investigated within the context of a ,-hairpin peptide. Significant enhancement of the interaction and structural stabilization of the hairpin have been observed upon Lys methylation. Thermodynamic analysis indicates an increased entropic driving force for folding upon methylation of Lys residues. Comparison of lysine to analogues ornithine (Orn) and diaminobutyric acid (Dab) indicates that lysine provides the strongest cation,, interaction and also provides the most stable ,-hairpin due to a combination of side chain,side chain interactions and ,-sheet propensities. These studies have significance for the recognition of methylated lysine in histone proteins. [source]

Sequence dependence of ,-hairpin structure: Comparison of a salt bridge and an aromatic interaction

PROTEIN SCIENCE, Issue 12 2003
Sarah E. Kiehna
Abstract A comparison of the contributions and position dependence of cross-strand electrostatic and aromatic side-chain interactions to ,-sheet stability has been performed by using nuclear magnetic resonance in a well-folded ,-hairpin peptide of the general sequence XRTVXVdPGOXITQX. Phe,Phe and Glu,Lys pairs were varied at the internal and terminal non,hydrogen-bonded position, and the resulting stability was measured by the effects on ,-hydrogen and aromatic hydrogen chemical shifts. It was determined that the introduction of a Phe,Phe pair resulted in a more folded peptide, regardless of position, and a more tightly folded core. Substitution of the Glu,Lys pair at the internal position results in a less folded peptide and increased fraying at the terminal residues. Upfield shifting of the aromatic hydrogens provided evidence for an edge-face aromatic interaction, regardless of position of the Phe,Phe pair. In peptides with two Phe,Phe pairs, substitution with Glu,Lys at either position resulted in a weakening of the aromatic interaction and a subsequent decrease in peptide stability. Thermal denaturation of the peptides containing Phe,Phe indicates that the aromatic interaction is enthalpically favored, whereas the folding of hairpins with cross-strand Glu,Lys pairs was less enthalpically favorable but entropically more favorable. [source]

Elongation of the BH8 ,-hairpin peptide: Electrostatic interactions in ,-hairpin formation and stability

PROTEIN SCIENCE, Issue 7 2001
Marina Ramírez-Alvarado
Abstract An elongated version of the de novo designed ,-hairpin peptide, BH8, has allowed us to gain insight into the role of electrostatic interactions in ,-hairpin stability. A Lys,Glu electrostatic pair has been introduced by adding a residue at the beginning and at the end of the N-terminal and C-terminal strands, respectively, of the ,-hairpin structure, in both orientations. The two resulting peptides and controls having Ala residues at these positions and different combinations of Ala with Lys, or Glu residues, have been analyzed by nuclear magnetic resonance (NMR), under different pH and ionic strength conditions. All of the NMR parameters, in particular the conformational shift analysis of C, protons and the coupling constants, 3JHN,, correlate well and the population estimates are in reasonable agreement among the different methods used. In the most structured peptides, we find an extension of the ,-hairpin structure comprising the two extra residues. Analysis of the pH and salt dependence shows that ionic pairs contribute to ,-hairpin stability. The interaction is electrostatic in nature and can be screened by salt. There is also an important salt-independent contribution of negatively charged groups to the stability of this family of ,-hairpin peptides. [source]

Effects of Chain Length and N-Methylation on a Cation,, Interaction in a ,-Hairpin Peptide

Time-averaged predictions of folded and misfolded peptides using a reduced physicochemical model

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2008
Oliver J. Clarke
Abstract Energy-based methods for calculating time-averaged peptide structures are important for rational peptide design, for defining local structure propensities in large protein chains, and for exploring the sequence determinants of amyloid formation. High-end methods are currently too slow to be practicable, and will remain so for the foreseeable future. The challenge is to create a method that runs quickly on limited computer resources and emulates reality sufficiently well. We have developed a simplified off-lattice protein model, incorporating semi-empirical physicochemical potentials, and combined it with an efficient Monte Carlo method for calculating time-averaged peptide structures. Reasonably accurate predictions are found for a set of small ,-helical and ,-hairpin peptides, and we demonstrate a potential application in measuring local structure propensities in protein chains. Time-averaged structures have also been calculated for a set of small peptides known to form ,-amyloid fibrils. The simulations were of three interacting peptides, and in each case the time-averaged structure describes a three-stranded ,-sheet. The performance of our method in measuring the propensities of small peptides to self-associate into possible prefibrillar species compares favorably with more detailed and CPU-intensive approaches. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source]

Applications of model ,-hairpin peptides

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2004
Carol E. Stotz
Abstract In recent years, ,-hairpin peptides have been studied in great detail. Much of the focus has been on the thermodynamic stability of ,-hairpin structure. Structural measurements have been conducted with nuclear magnetic resonance, with additional information obtained from circular dichroism, Fourier transform infrared, and molecular dynamic simulation studies. Point mutations, both in the ,-strands and in the turn region, have systematically explored the role of turn sequence, side-chain,side-chain interactions, intramolecular hydrogen bonding, and ,-strand length on ,-hairpin peptide conformational stability. In addition to studying the elements of structural stability independently, the cooperative nature of the individual components to combine to form the overall structure has also been investigated. Because the ,-hairpin peptides often spontaneously form their conformation, they have begun to serve as models for studying peptide binding and therapeutic agents. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2881,2894, 2004 [source]

Elongation of the BH8 ,-hairpin peptide: Electrostatic interactions in ,-hairpin formation and stability

Molecular Conformation and Packing of Peptide , Hairpins in the Solid State: Structures of Two Synthetic Octapeptides Containing 1-Aminocycloalkane-1-Carboxylic Acid Residues at the i+2 Position of the , Turn

CHEMISTRY - A EUROPEAN JOURNAL, Issue 12 2005
Veldore Vidya Harini
Abstract Peptide ,-hairpin formation is facilitated by centrally positioned D -Pro-Xxx segments. The synthetic peptides Boc-Leu-Phe-Val- D -Pro-Ac6c-Leu-Phe-Val-OMe (1) and Boc-Leu-Phe-Val- D -Pro-Ac8c-Leu-Phe-Val-OMe (2) were synthesized in order to explore the role of bulky 1-aminocycloalkane-1-carboxylic acid residues (Acnc, where n is the number of carbon atoms in the ring), at the i+2 position of the nucleating , turn in peptide , hairpins. Peptides 1 and 2 crystallize in the monoclinic space group P21 with two molecules in the asymmetric unit. The crystal structures of 1 and 2 provide conformational parameters for four peptide hairpin molecules. In all cases, the central segments adopts a type II, ,-turn conformation, and three of the four possible cross-strand hydrogen bonds are observed. Fraying of the hairpins at the termini is accompanied by the observation of NH,,,, interaction between the Leu(1)NH group and Phe(7) aromatic group. Cross strand stabilizing interactions between the facing residues Phe(2) and Phe(7) are suggested by the observed orientation of aromatic rings. Anomalous far-UV CD spectra observed in solution suggest that close proximity of the Phe rings is maintained even in isolated molecules. In both peptides 1 and 2, the asymmetric unit consists of approximately orthogonal hairpins, precluding the formation of a planar ,-sheet arrangement in the solid state. Solvent molecules, one dioxane and one water in 1, three water molecules in 2, mediate peptide association. A comparison of molecular conformation and packing motifs in available ,-hairpin structures permits delineation of common features. The crystal structures of ,-hairpin peptides provide a means of visualizing different modes of ,-sheet packing, which may be relevant in developing models for aggregates of polypeptides implicated in disease situations. [source]